"Because Y-142 and CRM197 bind to HB-EGF and cetuximab binds to EGFR, it is difficult to directly compare the amino acids used for binding by each reagent to inhibit the sHB-EGF-EGFR interaction."
"This data suggested that sHB-EGF interacts with EGFR during its translocation to the nuclear envelope."
"EGFR is one of the HB-EGF receptors, and the binding of sHB-EGF to EGFR leads to phosphorylation of EGFR and activation of its downstream signaling."
"Pro-HB-EGF is cleaved at the cell surface to yield the soluble form of HB-EGF (sHB-EGF). xref Subsequently, sHB-EGF directly binds to both EGF receptor (EGFR) and ErbB4, xref which triggers receptor dimerization and activates downstream kinases, including extracellular signal-regulated kinase (ERK), JNK, and phosphatidylinositol 3-kinase (PI3K). xref It has been reported that osteoblast differentiation and bone formation can be regulated by EGFR signaling."